Chromosomal translocations fuse sections of two heterologous chromosomes or two separated regions on homologous chromosomes. Other than from resection at a fixed break, such junctions are expected to result mostly from end-joining of double-strand breaks (DSBs) to other genomic DSBs. DSBs can arise from a number of stresses and sources. The frequency and location of such DSBs and resulting chromosomal translocations is of particular interest in cancer, V(D)J recombination, and within the context of the use of engineered nucleases, e.g., for gene therapy. Existing methods of high-throughput genome-wide translocation sequencing (HTGTS) uses engineered “bait” DSBs to detect other “prey” cellular DSBs genome-wide.